Aryloxyphenylpropylamines their preparation and use

Abstract

Novel aryloxyphenylpropylamines having the formula ##STR1## wherein X is H, cyano, halogen, halogenoalkyl, C 1-6 -alkoxy, C 1-6 -alkyl, C 1-5 -alkanoyl, C 3-5 -alkylene, aryloxy or aralkoxy, and R is 3,4-methylenedioxy, aryl or heteroaryl which are optionally substituted with one or more cyano, halogeno, C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -alkenyl, trifluoromethyl, C 3-5 -alkylene, aryloxy or aralkoxy; and R 1 and R 2 independently is C 1-10 -alkyl, C 3-7 -cycloalkyl, C 2-10 -alkenyl, C 3-6 -cycloalkyl-C 1-5 -alkyl, optionally substituted with C 1-5 -alkoxy or cyano; R 1 and R 2 may together form a carbocyclic ring and a salt thereof with a pharmaceutically acceptable acid, provided however that R 1 is not C 3-7 -cycloalkyl, C 1-10 -alkyl, or alkenyl which may be straight, branched or cyclic, unsubstituted or substituted with C 1-4 -alkoxy, aryloxy or cycloalkyl or cycloalkylalkyl, when X is H and R 2 is a methyl group. The novel compounds are useful in the treatment of anoxia, migraine, ischemia, epilepsy, traumatic injury and neurodegenerative diseases.

What is claimed is: 
     
       1. A method of treating calcium overload in brain cells of mammals comprising administering an effective amount of a compound of formula I ##STR9## wherein X is H, cyano, halogen, C 1-6  -alkoxy, C 1-6  alkyl or C 3-5  -alkylidene; R is 3,4-methylenedioxyphenyl and phenyl which are optionally substituted with cyano, halogen, C 1-6  -alkyl, C 1-6  -alkoxy, C 2-6  -alkenyl, trifluoromethyl or C 3-5  -alkylidene; and   R 1  and R 2  independently are C 1-10  -alkyl, C 3-7  -cycloalkyl, C 2-10  -alkenyl or C 3-6  -cycloalkyl-C 1-5  -alkyl which are optionally substituted with C 1-5  -alkoxy or cyano;   provided that R 1  is not C 3-7  -cycloalkyl, C 1-10  -alkyl or C 2-10  -alkenyl which are optionally substituted with C 1-4  -alkoxy, when X is H and R 2  is a methyl group; or a pharmaceutically acceptable salt thereof.   
     
     
       2. The method according to claim 1, wherein the compound of formula I is 3-(4-cyanophenyl)-N,N-dimethyl-3-(5,6,7,8-tetrahydro-2-naphthoxy) propylamine or a pharmaceutically acceptable salt thereof. 
     
     
       3. The method according to claim 1, wherein the compound of formula I is N-butyl-N-methyl-3-(4-fluorophenyl)-3-(5,6,7,8-tetrahydro-2-naphthoxy) propylamine or a pharmaceutically acceptable salt thereof. 
     
     
       4. The method according to claim 1, wherein the compound of formula I is N,N-dibutyl-3-(4-trifluoromethylphenoxy)-3-phenylpropylamine or a pharmaceutically acceptable salt thereof. 
     
     
       5. The method according to claim 1, wherein the compound of formula I is N-cyclopropylmethyl-N-methyl-3-(4-fluorophenyl)-3-(5,6,7,8-tetrahydro-2-naphthoxy) propylamine or a pharmaceutically acceptable salt thereof.